Ines Hardy

Selenium Supplementation in the Critically Ill

Selenium (Se) is an essential trace element with antioxidant, immunological, and anti-inflammatory properties, which are attributed to its presence in selenoproteins, as the 21st amino acid selenocysteine. These selenoenzymes are involved in redox signaling, antioxidant defense, thyroid hormone metabolism, and immune responses. Dietary intakes differ considerably between geographical regions, due to variability of the Se food content, leading to differences in dietary reference intakes and toxicity cautions. Critical illness with systemic inflammatory response syndrome (SIRS) is characterized by Se depletion with high morbidity and mortality. Se status correlates well with clinical outcome in SIRS and may be useful as an early predictor of survival. Several investigators have evaluated the benefits of Se supplementation for the critically ill, either as monotherapy or in an antioxidant micronutrient combination. Pharmaconutrition, with high-dose Se (from 500-1600 µg/d) involving an initial loading bolus, followed by continuous infusion, appears to be safe and efficacious, with evidence that it can improve clinical outcome by reducing illness severity, infectious complications, and decreasing mortality in the intensive care unit (ICU). We now have a clearer understanding of the pharmacokinetics of the initial and transient pro-oxidant effect of an intravenous bolus of selenite and the antioxidant effect of continuous infusion. Better biomarkers to ascertain optimum Se requirements for individual patients are now needed, and clinical practice guidelines need improvement. Nevertheless, sufficient evidence is available to consider initiating high-dose intravenous Se therapy routinely in critically ill SIRS patients, immediately on admission to the ICU.

Is manganese an essential supplement for parenteral nutrition

Purpose of reviewTo summarize the role of the essential trace element, manganese, its potential toxicity, monitoring methods and dosage recommendations for nutrition support. Recent findingsParenteral nutrition usually contains manganese as part of a fixed concentration multiple trace element supplement. Recent literature identifies potential problems in this approach and reports toxic symptoms resulting from hypermanganesaemia in paediatric and long-term home patients. Elimination by the hepatobiliary system is frequently impaired, and parenteral administration bypasses the regulatory mechanisms of homeostasis. Together with occasional oral intake and product contamination, this can lead to brain accumulation and neurotoxicity, with individual responses to supplementation difficult to predict. Regular monitoring is recommended, but plasma and serum analyses are poor indicators of body stores. Whole blood concentrations are more accurate and correlate with signal intensity of MRI. We have identified a need for individual trace element additives to be more widely available and for multitrace element products to be reformulated. There is now a persuasive argument for not routinely adding manganese to parenteral nutrition admixtures. SummaryHigh intravenous doses of manganese can lead to neurotoxicity. Current dosage guidelines and trace element formulations need revision. Frequent monitoring to identify tissue accumulation is recommended for paediatric and long-term home parenteral nutrition patients.

Nutraceuticals--a pharmaceutical viewpoint: part II.

Purpose of reviewTo review pharmaceutical and pharmacological issues relating to the benefits and risks associated with the use of naturally sourced nutraceuticals when administered singly or in combinations. Recent findingsThe application of vegetable extracts or dietary supplementation with selenium or antioxidant vitamins results in positive benefits on immunity and other phenomena associated with chronic diseases, ageing and cancer. However, there appear to be no cardiovascular benefits from vitamin mixtures, which may in fact cause harm. Therefore, although recent publications have increased our understanding of the metabolic actions of nutraceuticals, learning to use them to the best advantage is going to require products with uniform and consistent quality. Unfortunately, a single purified substance will not always have the same antioxidant activity, nor provide the same clinical benefits as nutraceutical mixtures and combinations occurring in natural extracts. In order to perform first-class clinical studies to determine safety and efficacy, the stability, compatibility and other pharmaceutical variables inherent in many of these combination products will have to be better controlled. SummaryNutraceuticals have potent biological actions. Their use is increasing dramatically, and there is growing evidence of clinical benefits. No medicinal products are completely safe so their risks need to be characterized and controlled. Imposing pharmaceutical levels of control and regulation would increase costs and reduce patient access to new products, but the evidence is compelling that closer monitoring of raw materials, processing and formulation will be required to maximize the benefits and minimize the risks.

Can Glutamine Enable the Critically Ill to Cope Better With Infection

8% in patients receiving IV therapy, and one-third of BSIs are related to central venous lines used for parenteral nutrition (PN) or other intensive care therapies. Hospitalacquired infections (HAIs) affect 10% of patients admitted to acute hospitals in the United Kingdom, with an estimated annual cost of

Antimicrobial effects of arginine and nitrogen oxides and their potential role in sepsis.

2 billion. Between 10% and 35% of intensive care unit (ICU) patients in the United States develop nosocomial infections, of which 10% are BSIs. 2 With an attributable hospital mortality of 15%, which is rising annually, 3 this represents the eighth leading cause of death. 4 Extremely sick patients represent only about 10% of the ICU population but in surgical ICUs (SICUs), they exhibit the highest risk of HAI. 5 BSIs worsen the severity of the patient’s underlying disease, prolong hospitalization by at least 4 days, 6 and are expensive to treat. Nosocomial infections are more likely in long-stay patients who are taking longer to recover before leaving the SICU. Staphylococcus epidermidis, Staphylococcus aureus, and Staphylococcus enterococci are the bacteria most frequently implicated, 1 while Candida albicans is the most common fungal organism, found among normal flora of the GI tract and vagina. 7 Candida infection is generally nosocomial and accounts for many infections. Almost half the patients in the ICU stay longer than 5 days and suffer from 1 or more infections, of which 17% are fungal. Infection is thus closely related to the duration of ICU stay and has long been associated with increased morbidity and mortality. 8

Selenium: The Se-XY nutraceutical

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